In organisms such as Methanosarcina barkeri that incorporate the modified amino acid pyrrolysine (Pyl) into certain methylamine methyltransferases, an unusual tRNAPyl, with a CUA anticodon, can be charged directly with pyrrolysine by this class II aminoacyl---tRNA ligase. The enzyme is specific for pyrrolysine as substrate as it cannot be replaced by lysine or any of the other natural amino acids [1].